Comparative genomics of NAD biosynthesis in cyanobacteria
Comparative genomics of NAD biosynthesis in cyanobacteria
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DOI：
10.1128/jb.188.8.3012-3023.2006
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发表时间：
2006-04-01
影响因子：
3.2
通讯作者：
Osterman, AL
中科院分区：
文献类型：
--
作者：
Gerdes, SY;Kurnasov, OV;Osterman, AL
NAD（P）辅因子的生物合成对蓝藻具有特殊的重要性，因为它们在光合作用和呼吸作用中起作用。尽管在理解NAD（P）的生物合成机制在一些模式生物中取得了重大进展，但对其在蓝藻中的实施知之甚少。我们通过比较基因组分析与在集胞藻属菌株PCC 6803的模型系统中的验证实验相结合来解决这个问题。使用SEED基因组平台（http：//theseed.uchicago.edu/FIG/index.egi）详细重建NAD（P）代谢子系统帮助我们准确地注释了具有当时可用的完全测序的基因组的13种蓝藻物种的整个集合中的相应基因。在这个不同的组中实施的操作变体的比较分析，使我们能够阐明保守的（从头和通用途径）和可变的（回收和抢救途径）这个子系统的方面。集中的遗传和生物化学实验证实了这个子系统的关键方面的几个命题。(i)slr 1691基因的产物是大肠杆菌基因nadE的同源物，含有额外的腈水解酶样N-末端结构域，是能够在体外利用谷氨酰胺作为酰胺供体的NAD合成酶。(ii)sII 1916基因的产物是E. coli基因nadD，是一种烟酸单核苷酸肽偏好性腺苷酰转移酶。该基因是生存所必需的，并且不能被替代的烟酰胺单核苷酸（NMN）-偏好腺苷酰转移酶（slr 0787基因）补偿。(iii)slr 0788基因的产物是烟酰胺偏好磷酸核糖基转移酶，其参与烟酰胺的两步非脱酰胺利用（NMN分流）的第一步。(iv)由保守基因簇slr 0787-slr 0788编码的该途径的生理作用可能在内源性产生的烟酰胺的再循环中，如该生物体不能利用外源性提供的烟酸所支持的。位置聚类和共生配置文件的各个基因在不同的细胞生物体的收集提供了证据的水平转移事件的进化史上的这一途径。
Biosynthesis of NAD(P) cofactors is of special importance for cyanobacteria due to their role in photosynthesis and respiration. Despite significant progress in understanding NAD(P) biosynthetic machinery in some model organisms, relatively little is known about its implementation in cyanobacteria. We addressed this problem by a combination of comparative genome analysis with verification experiments in the model system of Synechoeystis sp. strain PCC 6803. A detailed reconstruction of the NAD(P) metabolic subsystem using the SEED genomic platform (http://theseed.uchicago.edu/FIG/index.egi) helped us accurately annotate respective genes in the entire set of 13 cyanobacterial species with completely sequenced genomes available at the time. Comparative analysis of operational variants implemented in this divergent group allowed us to elucidate both conserved (de novo and universal pathways) and variable (recycling and salvage pathways) aspects of this subsystem. Focused genetic and biochemical experiments confirmed several conjectures about the key aspects of this subsystem. (i) The product of the slr1691 gene, a homolog of Escherichia coli gene nadE containing an additional nitrilase-like N-terminal domain, is a NAD synthetase capable of utilizing glutamine as an amide donor in vitro. (ii) The product of the sII1916 gene, a homolog of E. coli gene nadD, is a nicotinic acid mononucleotide-preferring adenylyltransferase. This gene is essential for survival and cannot be compensated for by an alternative nicotinamide mononucleotide (NMN)-preferring adenylyltransferase (slr0787 gene). (iii) The product of the slr0788 gene is a nicotinamide-preferring phosphoribosyltransferase involved in the first step of the two-step nondeamidating utilization of nicotinamide (NMN shunt). (iv) The physiological role of this pathway encoded by a conserved gene cluster, slr0787-slr0788, is likely in the recycling of endogenously generated nicotinamide, as supported by the inability of this organism to utilize exogenously provided niacin. Positional clustering and the cooccurrence profile of the respective genes across a diverse collection of cellular organisms provide evidence of horizontal transfer events in the evolutionary history of this pathway.